The MITO CERV-2 trial: A randomized phase II study of cetuximab plus carboplatin and paclitaxel, in advanced or...

Cervical cancer cells often express Epidermal Growth Factor Receptor (EGFR). Cetuximab (CET), an anti-EGFR antibody, can be safely combined with carboplatin (C) and paclitaxel (P), a standard treatment for advanced/recurrent cervical cancer (ARCC) patients.

ARCC patients, ECOG PS ≤ 1, were randomized to CP for 6 cycles with or without CET (400 mg/m² one week before starting CP, then 250 mg/m² weekly) until disease progression or unacceptable toxicity. Event-free survival (EFS) was the primary endpoint. With a 4.5 months expected median EFS and a 6.4 months predicted EFS (HR 0.70), 0.20 one-tailed α and 80% power, 89 events were required for the final intent-to-treat analysis.

108 patients were assigned to CP (n = 53) or CP-CET (n = 55). Median age was 50, 69% were PS0, 76% had recurrent disease, 91% had distant metastasis and 57% had received previous chemotherapy. After a median follow-up of 23 months, 102 patients had an event, 97 progressed and 61 died. Median EFS was 4.7 and 6.0 months (one-tail P = 0.43), median PFS was 5.2 and 7.6 months (one-tail P = 0.20) and median OS was 17.7 and 17 months (one-tail P = 0.27), with CP and CP-CET, respectively. There was no difference in the occurrence of severe adverse events, except for skin toxicity. Biomarker analysis, in a small subgroup of patients, suggests that PIK3CA mutation might be predictive of CET resistance.

CP-CET was not more active than CP alone in unselected ARCC patients.